Clinical Characteristics and Outcomes of Korean Patients with Lipoid Congenital Adrenal Hyperplasia: An Analysis of Data from the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) Cohort Study.

BACKGRUOUND: Clinical characteristics and follow-up outcomes were examined in Korean patients with lipoid congenital adrenal hyperplasia (LCAH) enrolled in the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) cohort.

METHODS

Thirty-one patients (classic LCAH [C-LCAH], n=29; nonclassic LCAH [NC-LCAH], n=2) from 10 centers were included. NC-LCAH was defined by any of the following: 46,XY karyotype with male external genitalia, no fludrocortisone use, or diagnosis after infancy.

RESULTS

Median age at diagnosis was 36.5 days (interquartile range [IQR], 14.6 to 120.5); salt-wasting occurred in 58.6% of patients, and skin hyperpigmentation was the most common clinical feature (71%). All C-LCAH patients (STAR variants: p.Q258*/p.Q258* [n=27], p.Q258*/p.Arg182His [n=1], p.Q258*/p.Arg182Cys [n=1]; karyotypes: 46,XX [n=17], 46,XY [n=12]) were diagnosed in infancy with a female phenotype. Among C-LCAH patients with 46,XX, 11 had spontaneous thelarche (median, 11.0 years; IQR, 8.2 to 12.2) and five reached menarche (median, 12.4 years; IQR, 11.9 to 13.2). Among eight C-LCAH-XX patients who underwent ultrasonography, three had unilocular ovarian cysts, including one rupture. Two NC-LCAH patients (p.Q258*/p.Val187Met and p.Ala218Val/p.Gly221Ser; both 46,XY) were diagnosed at 1.6 and 3.3 years with male external genitalia; one had spontaneous puberty at 10.6 years. Eight patients reached adult height (Z-score, 0.1; IQR, -0.9 to 1.2). The hydrocortisone dose was 21.7 mg/m2 (IQR, 14.9 to 26.5) at diagnosis and 17.3 mg/m2 (IQR, 13.9 to 22.7) at last follow-up (median age, 11.6 years; IQR, 8.9 to 17.4).

CONCLUSION

This is the first large-scale multicenter investigation in Korea reporting long-term outcomes of LCAH. Continued longitudinal follow-up focusing on pubertal development and reproductive outcomes is warranted.